Mare reproductive loss syndrome (MRLS) is a syndrome consisting of equine abortions and three related nonreproductive syndromes which occur in horses of all breeds, sexes, and ages. MRLS was first observed in the U.S. state of Kentucky in a three-week period around May 5, 2001, when about 20–30% of Kentucky's pregnant mares suffered abortions. A primary infectious cause was rapidly ruled out, and the search began for a candidate toxin. No abortifacient toxins were identified. In the spring of 2001, Kentucky had experienced an extraordinarily heavy infestation of eastern tent caterpillars (ETCs). An epidemiological study showed ETCs to be associated with MRLS. When ETCs returned to Kentucky in the spring of 2002, equine exposure to caterpillars was immediately shown to produce abortions. Research then focused on how the ETCs produced the abortions. Reviewing the speed with which ETCs produced late-term abortions in 2002 experiments, the nonspecific bacterial infections in the placenta/fetus were assigned a primary driving role. The question then became how exposure to the caterpillars produced these non-specific bacterial infections of the affected placenta/fetus and also the uveitis and pericarditis cases. Reviewing the barbed nature of ETC hairs (setae), intestinal blood vessel penetration by barbed setal fragments was shown to introduce barbed setal fragments and associated bacterial contaminants into intestinal collecting blood vessels (septic penetrating setae). Distribution of these materials following cardiac output would deliver these materials to all tissues in the body (septic penetrating setal emboli). About 15% of cardiac output goes to the late-term fetus, at which point the septic barbed setal fragments are positioned to penetrate placental tissues which lack an immune response. Bacterial proliferation, therefore, proceeds unchecked and the late-term fetus is rapidly aborted. Similar events occur with the early-term fetus, but as a much smaller target receiving an equivalently smaller fraction of cardiac output, the early-term fetus is less likely to be "hit" by a randomly distributing setal fragment. Since this MRLS pathogenesis model was first proposed in 2002, other caterpillar-related abortion syndromes have been recognized, most notably equine amnionitis and fetal loss in Australia, and more recently, a long-recognized relationship between pregnant camels eating caterpillars and abortions among the camel pastoralists in the western Sahara.
History What became MRLS was first noted on April 26, 2001, by Dr. Thomas Riddle of Lexington, Kentucky, who observed an unusual number of equine in utero early fetal deaths in 60-day-old fetuses he was examining by ultrasound for sex determination. These early fetal losses were soon followed by a sequence of numerous early and late fetal losses and, recognized somewhat later, coincident and relatively small numbers of pericarditis, unilateral uveitis, and encephalitis syndromes occurring in horses of all ages and sexes. The fetal loss numbers were large. During the three weeks around the first of May 2001, about 20–30% of Kentucky's pregnant mares suffered abortions. Of foals conceived in the spring of 2001, about 2000 were lost, the so-called early fetal losses (EFLs). Of foals conceived during the spring of 2000, and then close to term, at least 600 were lost, the so-called late fetal losses (LFLs). Based on these overwhelming reproductive losses, the syndrome was named the mare reproductive loss syndrome (MRLS). MRLS was defined as including four syndromes: (1) EFLs, (2) LFLs, (3) unique unilateral uveitis, and (4) pericarditis syndrome. An associated encephalitis syndrome was not included in the original case definition. The unusual pericarditis cases and the unique single-eye uveitis cases were observed in horses of all ages, breeds, and sexes, were independent of any state of pregnancy, and that they occurred at the same time as the early and late fetal loss syndromes. From the first, therefore, MRLS was clearly not simply a pregnancy-related syndrome. The total economic loss to Kentucky and the racing industry for the 2001 MRLS season has been estimated at $336–500 million. Coincident with the MRLS syndrome in May 2001, Kentucky was experiencing an extraordinarily heavy infestation of eastern tent caterpillars (ETCs). As part of an extensive and multifaceted investigation spearheaded by the University of Kentucky, a rigorous epidemiological survey by Dr. Roberta Dwyer and her associates soon confirmed an association of MRLS with the presence of the caterpillar. Yet to come, however, was scientific proof that the caterpillars were the cause of MRLS, and the proposed mechanism by which they affected horses.
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